PCS1055 diHCl is a potent, selective and competitive muscarinic M4 receptor blocker (antagonist) with IC50 of 18.1 nM and Kd of 5.72 nM. PCS1055 diHCl inhibits/disrupts the binding of the radioligand [3H]-NMS to the M4 receptor with Ki of 6.5 nM. The selectivity of PCS1055 diHCl for M4 receptors is more than 100 times that of M1, M3 and M5 receptors, and 30 times that of M2 receptors. PCS1055 diHCl is also a potent AChE inhibitor (antagonist) with IC50s of 22 nM and 120 nM for electric eel and human AChE, respectively.

Physicochemical Properties

Molecular Formula	C27H34CL2N4
Molecular Weight	485.491664409637
Exact Mass	484.216
CAS #	361979-40-0
Related CAS #	357173-55-8
PubChem CID	132470896
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	6
Heavy Atom Count	33
Complexity	525
Defined Atom Stereocenter Count	0
SMILES	Cl.Cl.N1(CC2C=CC=CC=2)CCC(CCNC2=CC3=C(C4C=CC=CC=4CCC3)N=N2)CC1
InChi Key	VSCSFYDNGYAWKG-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H32N4.2ClH/c1-2-7-22(8-3-1)20-31-17-14-21(15-18-31)13-16-28-26-19-24-11-6-10-23-9-4-5-12-25(23)27(24)30-29-26;;/h1-5,7-9,12,19,21H,6,10-11,13-18,20H2,(H,28,29);2*1H
Chemical Name	N-[2-(1-benzylpiperidin-4-yl)ethyl]-3,4-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-amine;dihydrochloride
Synonyms	PCS 1055; PCS-1055; PCS1055
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Furthermore, PCS1055 inhibits agonist-stimulated GTP-γ-[35S] binding, demonstrating its antagonistic effects on functional signaling. PCS1055 has a concentration-dependent inhibitory effect on G protein activation, with M4 receptors showing the greatest inhibitory effect. With binding preferences of 130, 31.2, 426, and >1000-fold and functional preferences of 255, 69.1, 342, and >1000-fold, PCS1055 was most effective against the M4 receptor subtype, according to both studies. According to [1], they are M1-, M2-, M3-, and M5 receptors.
ln Vivo	At the 30-minute mark, the male mice treated with PCS1055 (30 mg/kg; i.p.) exhibited maximal plasma levels, with a total plasma concentration of 45,100 nM and an unbound plasma concentration of 631 nM. At one hour, 11.8 nM of the maximal compound exposure was seen in the brain [1].
Animal Protocol	Animal/Disease Models: Male mice [1] Doses: 30 mg/kg Route of Administration: intraperitoneal (ip) injection (pharmacokinetic/PK/PK analysis) Experimental Results: Maximum plasma concentration was observed at the 30-minute time point, with a total plasma concentration of 45100 nM, unbound Plasma concentration is 631nM. The maximum compound exposure observed in the brain was 11.8 nM at 1 hour.
References	[1]. Characterization of PCS1055, a novel muscarinic M4 receptor antagonist. Eur J Pharmacol. 2016 Jul 5;782:70-6. [2]. Design, synthesis, and structure-activity relationships of a series of 3-[2-(1-benzylpiperidin-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors. J Med Chem. 2001 Aug 16;44(17):2707-18.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0598 mL	10.2989 mL	20.5977 mL
	5 mM	0.4120 mL	2.0598 mL	4.1195 mL
	10 mM	0.2060 mL	1.0299 mL	2.0598 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.